Psychopharmacology Rachad Rayess, M.D.

Outline Brain Anatomy Brain Development Neurophysiology of the Brain Neurotransmitters - types, pathways Pharmacokinetics and Pharmacodynamics Psychotropic Medications Psychiatric Illness and use of medications

Brain Anatomy

Brain Development

Grey Vs. White Matter

Neurophysiology Action Potential Neural Synapse Neurotransmitters

Dopamine (substantia nigra, ventral tegmentum) Serotonin (Raphe nuclei) Norepinephrine (locus coeruleus) Acetylcholine (brainstem) Glutamate GABA

Dopamine Pathways

Serotonin Pathways

Norepinephrine Pathways

Acetylcholine Pathways

Glutamate Pathways

GABAergic Pathways

Pathophysiology Psychosis: high dopamine Depression/Anxiety: low serotonin/norepinephrine ADHD: low dopamine

Pharmacokinetics and Pharmacodynamics

Pharmacokinetics: movement of the drug in the body what our body does with the drug Pharmacodynamics: how the drug works action of the drug on the human body

Administration Routes Intravenous Intraperitoneal Intramuscular Subcutaneous Oral (PO) Sublingual Inhalation Topical Intrarectal Intracranial

Drug Distribution Lipid solubility Blood-brain barrier

Drug Effectiveness and Drug Safety

Effects of Repeated Administration Tolerance Sensitization Withdrawal symptoms

Site of Drug action: Receptors Ion channels Intracellular proteins Effect on Receptors Agonist Antagonist Placebo effect

Psychotropic Medications

Stimulants Methylphenidates: Concerta, Focalin, Ritalin, Metadate, Methylin (chewable, solution), Daytrana (patch) Dextroamphetamines: Vyvanse, Adderall, Dexedrine Short-acting and long-acting preparations (XR) Increase dopamine and norepinephrine Treatment for ADHD/ADD

Stimulants Adverse Reactions: Dependency, abuse potential Psychosis, mania Myocardial infarction (heart attack), arrhythmia, stroke Seizures Growth suppression Common Reactions: Headache, dry mouth, abdominal pain, anorexia, nausea/vomiting, motor tics, dizziness, blood pressure changes, irritability

Non-stimulants Atomoxetine (Strattera) Inhibits norepinephrine reuptake Treatment for ADHD/ADD Black Box Warning: increased risk of suicidality Side effects: dry mouth, abdominal pain, nausea/vomiting, insomnia, abnormal dreams, appetite decrease, somnolence, fatigue, blood pressure and heart rate increase. Serious reactions: psychosis, aggressive behavior, stroke, seizures, liver toxicity, myocardial infarction (heart attack)

SSRIs Selective Serotonin Re-uptake Inhibitors: Fluoxetine (Prozac) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro) Paroxetine (Paxil)

SSRIs Indication: Depressive Disorders Generalized Anxiety Disorder Obsessive-compulsive Disorder Panic Disorder Black Box Warning: Increase suicidality risk Persistent Pulmonary Hypertension of theNewborn (PPHN)?

SSRIs Serious Adverse Reactions: Serotonin syndrome (life-threatening drug reaction) Neuroleptic malignant syndrome (severe drug reaction) Withdrawal syndrome Mania Anaphylactoid reactions (allergic reaction) Seizures Glaucoma (increased pressure in eye)

SSRIs CommonReactions: Nausea Headache Diarrhea Dizziness Dry mouth Tremor Libido decrease (low sexual interest)

SNRIs Serotonin Norepinephrine Re-uptake Inhibitors: Duloxetine (Cymbalta) Venlafaxine (Effexor) Not typically used in children: Growth suppression (Effexor) Seizures, hypertension, urinary retention, arrhythmia, hepatotoxicity, pancreatitis, glaucoma, bleeding

Other Antidepressants Bupropion (Wellbutrin) Inhibits uptake of Norepinephrine and Dopamine Caution if: eating disorder, seizure disorder Sometimes used for treatment of ADHD Mirtazapine (Remeron) Increases Serotonin and Norepinephrine Blocks Histamine receptors Tricyclic Antidepressants (TCAs) Rarely used

Lithium Alters neuronal sodium transport Increases production of neuroprotective proteins Treatment of Bipolar disorder --> Mood stabilizer First psychotropic medication to be discovered Requires blood level monitoring Affects thyroid, kidneys Ebstein’s Anomaly risk if taken during pregancy

Lithium Serious Reactions: Coma Seizures Arrhythmias (irreg heart beat), syncope (fainting) Hypothyroidism (low thyroid hormone levels) Hyperparathyroidism (high calcium levels) Pseudotumor cerebri (increased brain pressure) Diabetes insipidus (excessive thirst)

Lithium Common Reactions: Tremor Polyuria Diarrhea Nausea/Vomiting Drowsiness Muscle weakness Dry mouth Fatigue Blurred vision

Anti-epileptics Valproic Acid (Depakote) Carbamazepine (Tegretol) Oxcarbazepine (Trileptal) Lamotrigine (Lamictal) Mood stabilizers for treatment of Bipolar disorder Risk of congenital abnormalities if taken during pregnancy. Some need blood level monitoring (Depakote)

Anxiolytics Benzodiazepines Lorazepam (Ativan), alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium) Work on GABA receptors Inhibit neuron firing Paradoxical effect in children Sedation Dependence, Tolerance and Abuse potential

Alpha Agonists Clonidine (Kapvay) Guanfacine (Tenex, Intuniv) Block alpha2 pre-synaptic adrenergic receptors Decrease levels of norepinephrine Initial indication was for high blood pressure PTSD Aggression, agitation, insomnia ADHD (3rd line treatment)

Antipsychotics Typical Antipsychotics - also known as first generation Neuroleptics: Haloperidol (Haldol) Chlorpromazine (Thorazine) Thioridazine (Mellaril) Fluphenazine (Prolixin) Pimozide (Orap)

Antipsychotics Atypical Antipsychotics (2nd generation neuroleptics): Clozapine (Clozaril) Riserpidone (Risperdal) Aripiprazole (Abilify) Ziprazidone (Geodon) Quetiapine (Seroquel) Olanzapine (Zyprexa) Paliperidone (Invega) Asenapine (Saphris) Lurasidone (Latuda)

Typical Antipsychotics Block Dopamine receptors Extrapyramidal symptoms (stiffness) Tardive dyskinesia (involuntary muscle movements) Dystonia (acute muscle spasm) Akathisia (restlessness) Neuroleptic malignant syndrome (potentially lethal) Arrhythmias (irregular heart beat) Leukopenia/neurtopenia (low white cell count) Drowsiness, lethargy Anxiety, insomnia Hyponatremia (low sodium), seizures

Atypical Antipsychotics Less extrapyramidal symptoms (stiffness) Less tardive dyskinesia (involuntary movements) Weight gain Diabetes mellitus (high glucose levels) Dyslipidemia (high cholesterol and lipids) Akathisia (restlessness) Tremor (shaking) Fatigue, somnolence (feeling tired) Dizziness, headache Agranulocytosis (low white blood count)

Melatonin Hormone made by the pineal gland in the brain Regulates circadian rhythm (internal clock) Side effects: morning grogginess, vivid dreams or nightmares, low body temperature, stomach cramps, dizziness, headaches, irritability

Benadryl Antihistamine - antagonizes histamine receptors Has a sedative effect - used for insomnia/agitation Used as a PRN (as-needed) in hospital settings Side effect: drowsiness, dizziness, incoordination, headache, palpitations Paradoxical effect Tolerance issues

Psychiatric Illnesses Mental Retardation Pervasive Developmental Disorders Autistic Disorder Asperger’s Disorder PDD NOS Attention-deficit and Disruptive Behavior Disorders ADD/ADHD ODD Disruptive Behavior Disorder Tic Disorders Tourette’s Disorder

Psychiatric Illnesses Psychotic Disorders Schizophrenia Schizoaffective Disorder Mood Disorders Bipolar Disorder Depression Anxiety Disorders Generalized Anxiety Disorder PTSD OCD Panic Disorder

Psychiatric Conditions Not Treated by Meds Learning Disorders Somatoform Disorders Factitious Disorders Eating Disorders Personality Disorders Adjustments Disorders